Rona R J, Tanner J M
Arch Dis Child. 1977 Mar;52(3):197-208. doi: 10.1136/adc.52.3.197.
Information on height, sex, age, and condition of mothers' pregnancy and labour was obtained on all first- and second-degree relatives of 140 cases of idiopathic growth hormone deficiency (GHD). Less detailed information was available for 68 further cases, the two samples together constituting all cases from England and Wales treated under the Medical Research Council Clinical Trial of Human Growth Hormone up till 1974. Compared with the Perinatal Mortality survey of 1958, idiopathic GHD cases showed a significantly greater incidence of breech births (13-7%), of forceps deliveries especially in multiparae (5-6%), and of reported early vaginal bleeding (7-1%). The incidences of breech and forceps were both higher in cases with multiple pituitary hormone deficiency than in cases of 'isolated' GHD. The frequency of either breech or forceps was 43% in multiple and 20% in 'isolated' GHD. Heights of fathers and sibs of affected cases averaged the 50th centile; those of mothers the 35th centile. The ratio of boys to girls affected was 3-8. There were 4 families with more than one member affected; 4-5% of the brothers of probands were themselves affected, 2% of fathers and 1-5% of both sisters and mothers. In the world literature the sex ratio averages about 2-9 with little difference between series; the frequency of breech delivery averages 21% with large differences (2% to 50%) between series. A table of relative risks is given from which a screening procedure may be constructed; following 1% of selected births would give 10% of cases, and 20% of births 50% of cases. We propose a multifactorial aetiology for GHD which brings it into line with malformations such as anencephaly, cleft lip and palate, and pyloric stenosis. An underlying liability to the disease is postulated, continuously distributed in the population and depending on both polygenic and environmental factors among which sex and birth trauma are important. The disease becomes manifest when the liability value reaches a fixed threshold. On this assumption, heritability of idopathic GHD is approximately the same as that of coeliac disease, pyloric stenosis, and patent ductus.
收集了140例特发性生长激素缺乏症（GHD）患者所有一级和二级亲属的身高、性别、年龄以及母亲怀孕和分娩情况的信息。另外68例患者的信息则没那么详细，这两个样本共同构成了截至1974年在医学研究理事会人类生长激素临床试验中接受治疗的英格兰和威尔士的所有病例。与1958年的围产期死亡率调查相比，特发性GHD病例中臀位分娩（13.7%）、尤其是经产妇的产钳分娩（5.6%）以及早期阴道出血（7.1%）的发生率显著更高。多种垂体激素缺乏症患者的臀位和产钳分娩发生率均高于“孤立性”GHD患者。在多种垂体激素缺乏症患者中，臀位或产钳分娩的频率为43%，在“孤立性”GHD患者中为20%。患病患者的父亲和兄弟姐妹的身高平均处于第50百分位；母亲的身高平均处于第35百分位。患病男孩与女孩的比例为3:8。有4个家庭中有不止一名成员患病；先证者的兄弟中有4% - 5%自身患病，父亲中有2%患病，姐妹和母亲中有1.5%患病。在世界文献中，性别比例平均约为2:9，各系列之间差异不大；臀位分娩的频率平均为21%，各系列之间差异很大（2%至50%）。给出了一个相对风险表，据此可构建一种筛查程序；跟踪1%的选定出生儿将发现10%的病例，跟踪20%的出生儿将发现50%的病例。我们提出GHD的多因素病因学，使其与无脑儿、唇腭裂和幽门狭窄等畸形情况相符。假定存在该疾病的潜在易感性，在人群中呈连续分布，且取决于多基因和环境因素，其中性别和出生创伤很重要。当易感性值达到一个固定阈值时，疾病就会显现。基于这一假设，特发性GHD的遗传度与乳糜泻、幽门狭窄和动脉导管未闭的遗传度大致相同。
